TABLE 3.
Genotypic changes of AG-021541-resistant replicon cell lines
| Amino acid change(s) | No. of cell lines with amino acid change(s) by selection method and AG-021541 concna
|
||||
|---|---|---|---|---|---|
| Serial passage
|
Direct colony formation
|
||||
| 1.6× EC90 | 3.2× EC90 | 6.4× EC90 | 3× EC90 | 6× EC90 | |
| M423T | 2 | 6 | 2 | 2 | 4 |
| M423T, A421V | 1 | ||||
| M423T, K535N | 1 | 1 | |||
| M423T, T19P | 1 | ||||
| M423V | 1 | 1 | 1 | ||
| M423V, V147I | 1 | ||||
| M423I | 1 | ||||
| M426T | 3 | ||||
| I482S | 1 | ||||
| I482S, A421V | 1 | ||||
| I482S, I432V, Y587C | 1 | ||||
| I482T | 1 | ||||
| I482T, K81N | 1 | ||||
| V494A | 1 | ||||
| V494A, K50R | 1 | ||||
| Total no. of lines | 9 | 8 | 7 | 6 | 5 |
a
RNA was extracted from stable cell lines obtained at various concentrations of AG-021541 either by serial passages or direct colony formation and subjected to RT-PCR amplification and population sequencing of the NS5B region.